炎症性腸疾患におけるチオプリンの治療薬のモニタリングと薬剤遺伝学:国際ガイドラインの見直し
Ahmed B Bayoumy1,2, Luc J J Derijks3,4, Nanne K H de Boer1,2
1Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Therapeutic drug monitoring
|August 29, 2025
まとめ
炎症性腸疾患 (IBD) のチオプリン療法に関するグローバルガイドラインは,有意な変化を示しています. 将来の勧告には,治療を最適化し,毒性を減らすためにNUDT15試験と代替モニタリング方法が含まれます.
科学分野:
- ファルマゲノミクス
- 胃腸内科
- 薬物の代謝
背景:
- チオプーリン (アザチオプリン,メルカプトプーリン,チオグアニン) はIBDの重要な維持療法です.
- ティオプーリンの代謝の個別の変動は,有効性と安全性に影響します.
- 治療薬モニタリング (TDM) と薬剤遺伝学は,チオプリン治療の最適化に不可欠です.
研究 の 目的:
- IBDにおけるチオプーリンのTDMと薬理学に関する国際ガイドラインを比較する.
- 現在のTDMの実践における世界的な格差を特定する.
主な方法:
- 世界各地の国際ガイドラインの概要
- 分析は,代謝物モニタリング,TPMT,およびNUDT15検査の推奨に焦点を当てた.
主要な成果:
- 23 ガイドラインは,TDMの勧告の有意な変動を示した (推奨の65%).
- TPMT検査は広く推奨されています (74%),しかしその有用性はアジア人群で議論されています.
- NUDT15検査は,特にアジア系およびヒスパニック系の人々の骨髄毒性の予測における重要性にもかかわらず,過小評価されています (13%).
結論:
- IBDにおけるチオプリンTDMと薬学遺伝子のグローバル慣行は矛盾しています.
- 限られたNUDT15の勧告と資源の制限は,一貫した臨床使用を妨げています.
- 将来のガイドラインには,NUDT15テストと代替モニタリング戦略を含む費用対効果の高い薬剤ゲノミクスを統合する必要があります.
関連する概念動画
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
264
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
264
Inflammatory Bowel Disease IV: Pharmacological Management
185
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
185
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
230
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
230
Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
413
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
413
Drugs for Treatment of Ulcerative Colitis in IBD
236
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
236
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
201
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
201


